Axis I and II comorbidity in adults with ADHD.

Ongoing debate over the validity of the attention-deficit/hyperactivity disorder (ADHD) construct in adulthood is fueled in part by uncertainty regarding implications of potentially extensive yet incompletely described comorbid Axis I and II psychopathology. Three hundred sixty-three adults ages 18 to 37 completed semistructured clinical interviews; informants were also interviewed, and best estimate diagnoses were obtained. Results were as follows: First, ADHD combined type (ADHD-C) had an excess of externalizing and internalizing Axis I disorders, suggesting a gradient-of-severity relationship between it and ADHD inattentive type (ADHD-I). Second, ADHD-C and ADHD-I did not differ in frequency of Axis II disorders. Third, however, ADHD overall was associated with increased rates of Axis II disorders, compared with rates in non-ADHD control participants, including both Cluster B (primarily borderline personality disorder) and Cluster C disorders. Fourth, ADHD incrementally accounted for clinician-rated global assessment of functioning scores above and beyond comorbid conditions or symptoms on either Axis I or Axis II. Results further inform nosology of ADHD in adults.

Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin.

The aim of this multicenter randomized trial was to compare carboplatin (400 mg/m2) and cisplatin (100 mg/m2) in patients with untreated advanced epithelial ovarian cancer. Toxicity and treatment efficacy assessed by pathological response rate, progression-free survival, and survival were the endpoints of the study. One hundred seventy-three patients with advanced epithelial ovarian cancer, F.I.G.O. (International Federation of Gynecology and Obstetrics) stage III and IV were accrued in the trial. The median follow-up time was 15 months (maximum, 34); three patients in each treatment arm were not eligible (four, nonepithelial ovarian cancer type; one, no data, and one, stage II). Patient characteristics were similar in the two groups. In the carboplatin-treatment arm, the overall pathological response rate was 57.3% and the complete pathological response rate was 26.8%. In the cisplatin-treatment arm, the overall pathological response rate was 71.6% and the complete pathological response rate was 24.7%. There was no statistical difference in the two arms in survival or progression-free survival. Cisplatin was more nephrotoxic while carboplatin induced a higher degree of myelosuppression, especially thrombocytopenia; however, severe hematological toxicity was seldom observed. Carboplatin is a cisplatin analog with definite activity in ovarian cancer, but it is more active than the parent compound. Because of less nonhematological toxicity, carboplatin is undoubtedly a useful substitute in patients who cannot be given cisplatin. Further experience is needed to indicate whether or not carboplatin should completely displace cisplatin in the clinical treatment of ovarian cancer.

Steroid receptors in epithelial ovarian carcinoma: relation to clinical parameters and survival.

Estrogen receptor (ER) and progestin receptor were measured in samples of tumors obtained at first laparotomy from 97 previously untreated patients suffering with a primary ovarian epithelial tumor, for whom a 3-year follow-up was available. The presence or absence of steroid receptors (threshold arbitrarily fixed at 10 fmol/mg of cytoplasmic protein) was determined by the dextran coated charcoal method and related to a number of patient characteristics such as the residual disease (cutoff, 2 cm), histological type, International Federation of Gynecologists and Obstetricians grade and stage, and age. Results were analyzed by univariate and multivariate methods. (a) The tumor ER positivity was associated with better survival; progestin receptor showed a similar trend but did not reach statistical significance. (b) After stratification for residual tumor the association ER positivity/better survival was still statistically significant in the subset of patients with residual tumor greater than 2 cm. (c) When the median survival times were considered it became apparent that progestin receptor absence nullified the effect associated with positive ER. (d) Multivariate analysis confirmed that among the variables considered the main determinants of prognosis were the size of the residual tumor, serous histological type, and positive ER.

Cerebrospinal fluid HIV-1 RNA levels: correlation with HIV encephalitis.

OBJECTIVE: Neuropathological abnormalities induced by HIV-1 are not always predictable on the basis of the presence of HIV-related neurological symptoms. HIV-1 RNA load was measured in the cerebrospinal fluid (CSF) of HIV-infected patients to verify whether it could be a marker of HIV-induced neuropathology. DESIGN AND METHODS: Histopathological and immunohistochemical examination of the brain for HIV-1 p24 antigen was performed in 50 HIV-infected patients with neurological symptoms; patients were defined as having HIV encephalitis in the presence of HIV-related lesions or HIV-1 p24 antigen-positive cells. Quantitative polymerase chain reaction for HIV-1 RNA was retrospectively applied to CSF samples that had been drawn 1-60 days prior to death from these 50 patients; paired plasma samples of 28 patients were also analysed. RESULTS: The CSF HIV-1 RNA copy numbers were significantly higher in 22 patients with HIV encephalitis than in 28 patients without (median, 4.77 log10 versus 3.45 log10 copies/ml; P = 0.0003). No correlation was found between CSF HIV-1 RNA load and the presence of opportunistic brain pathologies at post-mortem examination or between HIV-1 RNA loads in paired CSF and plasma samples. CONCLUSIONS: High CSF HIV-1 RNA levels are associated with HIV encephalitis, regardless of the presence of opportunistic brain diseases or HIV-1 RNA levels in plasma. Quantitative CSF HIV-1 RNA may therefore be used as a specific marker of HIV-induced neuropathology.

Cisplatin versus carboplatin in combination with mitomycin and vinblastine in advanced non small cell lung cancer. A multicenter, randomized phase III trial.

BACKGROUND: In advanced not selected NSCLC chemotherapy achieved an advantage of approximately 1-2 months on median survival versus best supportive care. Chemotherapy seems to improve symptoms control, even if randomised studies with quality of life as first endpoint are lacking and often chemotherapy toxicity compromises the frail cost/benefit ratio. The aim of the present study is to evaluate the impact on QoL, substituting cisplatin, a pivot drug in NSCLC therapy, with carboplatin, an analogue with an improved toxicity profile. The combination of cisplatin with Mitomycin and Vinblastine was one of the most frequently used in the palliative setting at the time of design of our study. METHODS: Patients were randomized to receive MVP regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Cisplatin 100 mg/m2 d1) or MVC regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Carboplatin 300 mg/m2 d1) every 3 weeks. The QoL was evaluated by the Spitzer QL-Index and by the EORTC QLQ-C30+LC 13 questionnaires before chemotherapy, after one cycle, after three cycles, and then every 6 weeks in the first 6 months and every 3 months thenafter. RESULTS: From September 1994 to July 1997, 153 consecutive patients were randomized to MVP (75 patients) or MVC arm (78 patients). Despite difficulties in carrying out and analysing QoL items in such patients, the global QoL evaluated by the Spitzer's questionnaire suggested an advantage for MVC regimen (P=0.05) and a significant difference was observed in global health subdomain (P=0.04). The disease-related symptoms improved with time, and the benefits lasted for the entire treatment period. When evaluated with the EORTC questionnaire there was significantly less nausea and vomiting (P=0.0001), appetite loss (P=0.01), insomnia (P=0.03), constipation (P=0.01) and peripheral neuropathy (P=0.01) in favour of MVC, and a trend for less hair loss (P=0.05). The advantage lasted for all the duration of chemotherapy. No differences were observed in global quality of life subdomain (P=0.40) between the two regimen. QoL was the first endpoint and the statistical power was inadequate to assess other parameters. However, we reported a response rate of 43.1 and 38.6%, respectively, in MVP and MVC arm (P=0.59) and a median survival of 10.2 and 7.2 months, respectively, for cisplatin and carboplatin arm (P=0.39). CONCLUSIONS: The carboplatin containing regimen (MVC) has a significant better toxicity profile than the cisplatin containing (MVP) regimen as proven both by the EORTC questionnaires and by the WHO toxicity data reported by physicians. No significant differences in terms of response rate, time to progression and overall survival were observed between the two regimen. The two chemotherapy regimen showed a similar effectiveness in symptom palliation when evaluated with C30 addendum of EORTC QOL questionnaire. With the Spitzer's questionnaires a trend towards an improved quality of life index was observed during treatment with the carboplatin combination in comparison to the cisplatin combination. This difference, however, was not observed when the global quality of life was evaluated with the EORTC patients compiled questionnaires. A carboplatin containing regimen with better toxicity profile and a similar potentiality for symptoms control offers an option in comparison to similar cisplatin containing combinations in the palliative treatment of advanced NSCLC.

Quality of care assessment for breast cancer: how to measure benefits of prevention and therapy in oncology.

Over the last few years evaluation of quality of diagnostic and therapeutic care has become one of the most controversial and fastest growing fields of research in many areas of medicine. In this situation, oncology represents a model case as the conditions in which new therapeutic strategies are tested and implemented largely differ from routine practice, both in terms of availability of sophisticated technology and comparability of patient populations. The promising role of health care research for the understanding of factors through which research advances can be generalized to routine clinical practice has only recently being appreciated. From this point of view, the paper discusses the rationale and key findings of a multi-annual++ evaluation program on breast cancer care, underway in Italy since 1980. Special attention is given to how results (such as data on diagnostic delay or non-adherence to recommended treatment guidelines) can be used for the implementation of educational programs, controlled studies and ad hoc demonstration projects.

Attention deficit hyperactivity disorder in African American children: what can be concluded from the past ten years?

Samuel et al. [Samuel, V. J., Curtis, S., Thornell, A., George, P., Taylor, A., Brome, D. R., et al. (1997). The unexplored void of ADHD and African-American research: A review of the literature. Journal of Attention Disorders, 1(4), 197-207.] reviewed the literature on Attention Deficit Hyperactivity Disorder (ADHD) in African Americans, and found a paucity of research. The present review of 73 articles updates this assessment of available research and presents the current understanding of ADHD symptoms, assessment, diagnosis, and treatment in African American children ages 3-18. The authors conducted a qualitative review, as well as a mini meta-analysis of 5 studies of ADHD symptoms and 5 studies of ADHD diagnosis to clarify the question of racial differences in prevalence. African American youth had more ADHD symptoms (Cohen's d=0.45, p<.001), yet were diagnosed with ADHD only two-thirds as often as Caucasian youth (OR=.66, p<.001). This pattern was not explained by teacher rating bias or by SES, but may be influenced by parent beliefs about ADHD, higher rates of risk, and lack of treatment access and utilization. Lower treatment rates may be related to high rates of classroom behavior problems among African American youth. Findings also suggest that existing assessment tools may not adequately capture ADHD manifestation in African Americans. Findings highlight the need for more investigation and awareness of relevant cultural issues to inform a culturally competent approach to assessment, diagnosis, and treatment of ADHD in African Americans.

Clinical considerations on side-locked unilaterality in long-lasting primary headaches.

The relevance of side-locked unilateral pain (with no side shift) in diagnosing and differentiating primary long-lasting cephalgias such as tension headache and migraine is not clear. In the present study we have retrospectively examined the frequency of side-locked unilaterality in 1169 primary headache outpatients, whose pain duration was more than four hours. The cases were migraine (66%), tension-type headache (21%) and non-classifiable headache and atypical facial pain (not well defined headaches) (13%). The occurrence of side-locked unilateral pain was more frequent in migraine (17%) than tension headache (4%). However side-locked pain was found to be more frequent in patients with not-well-defined head pain (28%). Of the 1169 patients, 181 (15%) had side-locked unilateral pain: 70% of the 181 had migraine, 25% were not-well-defined head pain cases and 5% were tension-type headache cases. The high percentage of migraine cases in the side-locked unilateral group reflects the high proportion of migraine patients in the studied population.

Factors predicting response to chemotherapy and survival in patients with metastatic or recurrent squamous cell cervical carcinoma: a multivariate analysis.

Different regimens of chemotherapy have been proposed with contradictory results in patients with metastatic and recurrent cervical carcinoma: this seems mainly due to the lack of information about prognostic factors. This study was aimed at identifying significant factors predicting response to treatment and survival in 140 patients treated with chemotherapy for advanced, recurrent, or persistent squamous cell cervical carcinoma. Age, performance status, histologic type and grade, previous irradiation, interval from start of primary treatment and from irradiation, site of tumor, and therapeutic regimen were considered as possible predictors of response and survival in multivariate analysis. By multivariate analysis, only performance status and interval from irradiation (> 1 year) were significant in predicting response to treatment, whereas interval from first diagnosis, site of tumor, and response to treatment were significant in predicting survival. None of the polychemotherapy regimens significantly improved survival, despite a fourfold increase in the costs when compared to the least expensive monochemotherapy regimen. Ethical and economical concerns should be considered when proposing aggressive regimens to the patients. Factors such as site of tumor, performance status, and interval from first treatment should be considered as minimal requirements for correct evaluation of newly proposed regimens.

Valproate, carnitine metabolism, and biochemical indicators of liver function. Collaborative Group for the Study of Epilepsy.

The effects of valproate (VPA) on carnitine and lipid metabolism and on liver function were assessed in 213 age- and sex-matched outpatients from five centers, with the following distribution: VPA monotherapy, 54; VPA polytherapy, 55; other monotherapies, 51; and untreated, 53. Mean total and free carnitine levels were significantly lower in patients with polytherapy; acylcarnitine was significantly higher for VPA monotherapy and the ratio of acyl- to free carnitine was significantly higher in all patients receiving VPA. Ammonia, uric acid, and bilirubin were the only tests selectively impaired with VPA. A significant correlation was found between serum ammonia and VPA dosage. Glucose, beta-lipoproteins, triglycerides, acetacetate, and beta-hydroxybutyrate were unchanged in the four groups. Sex and age appeared to interact with total and free carnitine values. Adverse drug reactions were apparently unrelated to carnitine metabolism impairment. Only a few patients had abnormal carnitine values. Our data support the assumption that carnitine deficiency and abnormal liver function due to VPA are mostly subclinical events.

Selective elevation of monocyte chemotactic protein-1 in the cerebrospinal fluid of AIDS patients with cytomegalovirus encephalitis.

The CC chemokine monocyte chemotactic protein-1 (MCP-1) was markedly elevated in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-infected patients with cytomegalovirus (CMV) encephalitis. The MCP-1 CSF levels in CMV encephalitis were markedly higher than those in the CSF of HIV-infected patients with or without unrelated neurologic diseases, including progressive multifocal leukoencephalopathy, cryptococcal meningitis, toxoplasmic encephalitis, and primary lymphoma. Interleukin-8, RANTES, macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta were not substantially increased in the CSF of CMV encephalitis patients. High levels of MCP-1 may underlie monocyte recruitment and tissue damage in CMV encephalitis and may represent a rapid and useful tool in the diagnostic armamentarium for neurologic disorders associated with HIV infection.

Flow cytometric analysis of DNA content in human ovarian cancers.

A total of 155 samples from 101 patients with ovarian cancer were investigated using flow cytometry to evaluate the DNA index and the percentage of cells in the various cell cycle phases. Thirty-four samples were DNA diploid tumours, while the other 121 were DNA aneuploid tumours. The DNA index was very stable in different sites and over time in the same patient. Tumour stage and ploidy were significantly associated: stages III and IV tumour stage were more likely to be DNA aneuploid. Patients with residual tumour size at first surgery greater than 2 cm had a significantly larger number of DNA aneuploid than DNA diploid tumours. The DNA index was also related to the degree of differentiation of the tumours. The percentage of cells in the S phase of the cell cycle was significantly higher in DNA aneuploid and in poorly differentiated tumours than DNA diploid and well differentiated tumours. Multivariate analysis using the Cox model showed that the DNA index and the percentage of cells in S phase were not independent prognostic variables in this study. Prospectively collected data should be accumulated before assigning the DNA index an important role as a biological prognostic factor in ovarian cancer.

Critical review of the quality and development of randomized clinical trials (RCTs) and their influence on the treatment of advanced epithelial ovarian cancer.

Trials on chemotherapy of advanced ovarian cancer published between 1975-88 were systematically reviewed for quality (according to the method of Chalmers) and consistency of tested hypotheses with a view to a meta-analysis of all published studies in the field. Median overall, internal and external validity scores were 47%, 43% and 53%, respectively. No association was found between scores and key features of trials, such as percentage studies with significant results in response or survival or percentage studies with high or low follow-up retention (withdrawal rates less than or greater than or equal to 15%). Only 21% of trials reported a fully blind randomization procedure and only in 13% were drop-outs accounted for by the intent-to-treat method. Only 4 trials entered more than 150 patients per arm, a sample size consistent with detection of an absolute difference of 11% in mortality. The majority of trials (58%) investigated the role of combination regimens versus a single-agent control arm. The remaining trials tested different polychemotherapies. However, within these two general issues, treatment options were quite heterogeneous: seven subgroups were identified by whether cisplatin was present in either the treatment or the control arm. We conclude that the internal coherence and development of randomized clinical trials in advanced ovarian cancer and their methodologic soundness are quite poor. In this situation meta-analysis cannot go beyond a systematic attempt to answer a very general "treatment effectiveness" question.